Infantile onset spinocerebellar ataxia

Title

Other Names:

Ophthalmoplegia, hypotonia, ataxia, hypacusis, and athetosis; OHAHA syndrome; IOSCA; Ophthalmoplegia, hypotonia, ataxia, hypacusis, and athetosis; OHAHA syndrome; IOSCA; Spinocerebellar ataxia 8 (formerly); SCA8 (formerly); Spinocerebellar ataxia infantile with sensory neuropathy; Ophthalmoplegia - hypotonia - ataxia - hypoacusis - athetosis; Ophthalmoplegia-hypotonia-ataxia-hypoacusis-athetosis syndrome See More

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Metabolic disorders; Congenital and Genetic Diseases; Digestive Diseases; Metabolic disorders; Nervous System Diseases See More

This disease is grouped under:

Hereditary ataxia

Summary Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 1186

Disease definition

Infantile-onset spinocerebellar ataxia (IOSCA) is a hereditary neurological disorder with early and severe involvement of both the peripheral and central nervous systems. It has only been described in Finnish families.

Epidemiology

So far, 24 cases have been reported. In Finland, IOSCA has a population carrier frequency of more than 1:230.

Clinical description

IOSCA is characterized by very early ataxia, athetosis and reduced tendon reflexes (between 9 and 18 months of age). Ophthalmoplegia and sensorineural hearing loss are diagnosed in childhood. Other features, such as optic atrophy and sensory neuropathy with progressive loss of myelinated fibers in the sural nerve, appear later in the disease course. Hypogonadism may occur in females. Some patients show intellectual deficit. Epilepsy is a late manifestation and seizures may be life-threatening.

Etiology

IOSCA is caused by mutations in the C10orf2 gene (10q24) encoding the mitochondrial helicase Twinkle. The c.1523A>G (p.Y508C) causative mutation has been postulated to be a founder mutation. Twenty-one of the reported patients were homozygous for this mutation, and three were compound heterozygotes: c.952G>A/c.1523A>G (two patients) and c.1523A>G/c.1287C>T (one patient). The mutations lead to mtDNA depletion in the brain and the liver, but not in the muscle.

Diagnostic methods

The diagnosis is based on clinical and pathological findings. Studies of sural nerve biopsies reveal an early and rapidly progressive axonal neuropathy. Neuroimaging studies revealing cerebellar atrophy and genetic testing for the c.1523A>G mutation may also help to confirm the diagnosis.

Differential diagnosis

Differential diagnoses include early-onset cerebellar ataxias with sensory axonal neuropathy and epileptic encephalopathy, mitochondrial disorders with axonal neuropathy (such as Friedreich ataxia), progressive external ophthalmoplegia (PEO), juvenile- or adult-onset mitochondrial recessive ataxia syndrome (MIRAS), and POLG-related disorders (see theseterms).

Antenatal diagnosis

Prenatal testing may be available for families in which the disease-causing mutations have already been identified.

Genetic counseling

IOSCA is inherited in an autosomal recessive manner. Genetic counseling is an important clinical tool for preventing new cases, especially for couples with an affected first child: the risk of having an affected child in further pregnancies is 25%.

Management and treatment

IOSCA patients are often managed by a multidisciplinary team, involving a pediatrician, neurologist, psychiatrist, orthopedic surgeon, physical and occupational therapists, genetic counselor, and social worker. Treatment is symptomatic and may include: (1) hearing aids, speech therapy and sign language for deafness; (2) physical therapy, orthotic devices and orthopedic surgery for sensory axonal neuropathy; (3) walking aids, a wheelchair, physiotherapy and occupational therapy for ataxia; (4) antiepileptic drugs for seizures and (5) antipsychotics and antidepressants for psychiatric symptoms.

Prognosis

Prognosis is unfavorable. Patients are wheelchair-bound by adolescence. Early death is common due to severe seizures. The clinical course seems to be more rapid and severe (with death during infancy) in c.952G>A/ c.1523A>G compound heterozygotes.

Visit the Orphanet disease page for more resources.

Last updated: 4/9/2009

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of the autonomic nervous system		0002270
Ataxia		0001251
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Ophthalmoplegia	Eye muscle paralysis	0000602
Optic atrophy		0000648
Reduced tendon reflexes		0001315
5%-29% of people have these symptoms
Elevated hepatic transaminase	High liver enzymes	0002910
Percent of people who have these symptoms is not available through HPO
Areflexia	Absent tendon reflexes	0001284
Athetosis		0002305
Atrophy/Degeneration affecting the brainstem		0007366
Autosomal recessive inheritance		0000007
Cerebellar atrophy	Degeneration of cerebellum	0001272
Cerebral cortical atrophy	Decrease in size of the outer layer of the brain due to loss of brain cells	0002120
Clumsiness		0002312
Encephalopathy		0001298
Epilepsia partialis continua		0012847
Epileptic encephalopathy		0200134
Excessive daytime somnolence		0001262
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Hypergonadotropic hypogonadism		0000815
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Loss of ability to walk		0006957
Migraine	Intermittent migraine headaches Migraine headache Migraine headaches [ more ]	0002076
Muscle weakness	Muscular weakness	0001324
Muscular hypotonia	Low or weak muscle tone	0001252
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Poor eye contact		0000817
Progressive		0003676
Psychosis		0000709
Sensory axonal neuropathy		0003390
Specific learning disability		0001328
Status epilepticus		0002133

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 9/1/2018

Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

Spinocerebellar Ataxia: Making an Informed Choice about Genetic Testing is a booklet providing information about spinocerebellar ataxia and is available as a PDF document on the University of Washington Medical Center Web site. Click on the title above to view this resource.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

Coordination of Rare Diseases at Sanford (CoRDS) hosts a specific registry for patients with ataxia in partnership with the National Ataxia Foundation. The goal of the CoRDS registry is to connect as many patients and researchers as possible to help advance treatments and cures for rare diseases. The CoRDS registry is free for patients to enroll and for researchers to access.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Ataxia UK
12 Broadbent Close
London N6 5JW
United Kingdom
Telephone: 0845 644 0606 or 020 7582 1444
E-mail: helpline@ataxia.org.uk
Website: http://www.ataxia.org.uk

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Infantile onset spinocerebellar ataxia. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

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